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Biomedical subjects

C L Chan

Publications and source records attributed to C L Chan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Obesity and quality of life after primary hip arthroplasty.

In a prospective trial we studied 176 consecutive patients having a primary total hip arthroplasty to compare the quality of life before and after operation in non-obese and obese groups. We used a modified Harris hip score and the Rosser Index Matrix to generate these scores, and found that the median preoperative quality of life score for both groups was similar. During review, both groups showed a corresponding marked improvement in quality of life scores at one and three years. There was no statistically significant difference in the improvement in scores between the non-obese and obese groups. It appears that relative body-weight on its own does not influence the benefit derived from primary total hip arthroplasty.

Activities of Daily Living↗
PubMed1995

Discontinuous movements of DNA and RNA in RNA polymerase accompany formation of a paused transcription complex.

A central enigma of transcriptional regulation is how the normally efficient transcription elongation complex stops at pause and termination signals. One possibility, raised by the discovery that RNA polymerase sometimes contracts its DNA footprint, is that discontinuous movements contribute to recognizing these signals. We report that E. coli RNA polymerase responds to sequences immediately downstream and upstream from the his leader pause site by changing neither its downstream DNA contact nor its upstream RNA contact for 8 bp preceding the pause. This compressed complex isomerizes to a paused conformation by an approximately 10 bp jump of its downstream DNA contact and simultaneous extrusion of an RNA hairpin that stabilizes the paused conformation. We suggest pausing and termination could be alternative outcomes of a similar isomerization that depend on the strength of contacts to 3'-proximal RNA remaining after the jump.

Base Sequence↗
PubMed1995

Potential use of the intercostal artery as an in situ graft: a cadaveric study.

The third to eighth intercostal arteries (ICAs) were bilaterally dissected in 10 cadavers to assess their length and possible routes to coronary arteries if used as in situ grafts. The mean lengths for the intercostal arteries harvested were 27.0 +/- 2.9 cm on the left and 27.4 +/- 3.2 cm on the right. The shortest anatomic route to the coronary arteries of the in situ ICAs harvested was medial to the lung and either superior to or inferior to the hilum. By using either the superior or inferior routes in situ ICAs were long enough to reach the major coronary artery territories in all cadavers. The most suitable ICAs for grafting the coronary arteries and the shortest routes were as follows: left anterior descending--left fifth ICA by inferior route; circumflex coronary artery-left fifth ICA by inferior route; and right coronary artery-right seventh ICA by inferior route. We conclude that it is anatomically feasible to use the intercostal artery as an in situ graft in coronary artery operation.

Aged↗
PubMed1995

The desire for multiple births in couples with infertility problems contradicts present practice patterns.

Paradoxically, the attitude of infertility patients towards multiple births has never been investigated. We therefore generated a survey by questionnaire, which was sent to 3800 consecutive unselected couples with infertility problems: 582 responses were received (15% response rate) and analysed. The percentage distribution of the responses to 21 questions, addressing attitudes towards and knowledge about the risk of multiple gestations, was the main outcome. Worry about multiple births was expressed, independent of the number of multiples, although fear about multiple conceptions was rejected by a large majority (64%). The risk of a twin birth was not strongly perceived, but the perception of risk increased with increasing numbers of multiples: triplets (50-62%), quadruplets or more (71-72%). A desire for the conception of twins was expressed by 67-90% of couples, a desire for the conception of triplets was equally expressed and rejected, and for a multiple gestation beyond triplets was rejected by 73-82% of couples. Patients were educated about the risks of selective embryo reduction and responded in a bimodal fashion to the option of utilizing this procedure, with equal numbers being willing to consider or reject it. Age, parity and length of infertility did not affect the couples' worry or fear about multiples. The desire for twins and triples, however, was correlated significantly with age (twins, P = 0.032; triplets, P = 0.03); there was no such correlation for larger multiples. The length of infertility was correlated with a positive attitude towards multiples beyond triplets (P = 0.029) but was not correlated with a desire for twins or triplets. Prior parity did not affect the attitude towards multiples at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A comparison of two photon planning algorithms for 8 MV and 25 MV X-ray beams in lung.

We report results of a comparison of two photon planning algorithms, the Clarkson Scatter Integration algorithm and the Equivalent Tissue-air Ratio algorithm, using a simple lung phantom for 8 MV and 25 MV X-ray beams of field sizes 5 cm x 5cm and 10 cm x 10 cm. Central axis depth-dose distributions were measured with a thimble chamber or a Markus parallel-plate chamber. Dose profile distributions were measured with TLD rods and films. Measured dose distributions were then compared to predicted dose distributions. Both agorithms overestimate the dose at mid-lung as they do not account for the effect of electronic disequilibrium. The Clarkson algorithm consistently shows less accurate results in comparison with the ETAR algorithm. There is additional error in the case of the Clarkson algorithm because of the assumption of a unit density medium in calculating scatter, which gives an overestimate in the effective scatter-air ratios in lung. For a 5 cm x 5 cm field, the error of dose prediction (Dpredicted-Dmeasured) for 25 MV x-ray beam at mid-lung is 15.8% and 12.8% for Clarkson and ETAR algorithm respectively. At 8 MV the error is 9.3% and 5.1% respectively. In addition, both algorithms underestimate the penumbral width at mid-lung as they do not account for the penumbral flaring effect in low density medium. It is very important for medical physicists, radiation therapists and clinicians to be aware of the limitation of their radiotherapy treatment planning systems.

Algorithms↗
PubMed1994

GreA-induced transcript cleavage in transcription complexes containing Escherichia coli RNA polymerase is controlled by multiple factors, including nascent transcript location and structure.

The Escherichia coli GreA and GreB proteins induce cleavage of 3' fragments from nascent transcripts in halted transcription complexes. We have overproduced and purified the GreA protein and tested how it affects initiation, pausing, and termination by E. coli RNA polymerase. Recombinant GreA induced cleavage of two to three nucleotide fragments in two promoter-proximal complexes, whereas an apparently endogenous cleavage removed a single larger fragment. Both types of cleavage stopped once the transcript was shortened to approximately 10 nucleotides. However, during initiation, GreA induced cleavage of transcripts as short as four nucleotides, inhibiting their release as abortive products and stimulating both productive initiation and "primer-shifting" at a weak promoter. GreA induced repetitive cleavage over a long distance in complexes containing a long G-less nascent transcript. However, reverse translocation was inhibited in transcription complexes that contained a G-rich, C-less nascent transcript. Substituting IMP for GMP in the transcript relieved inhibition. Finally, GreA had little effect on transcription through the his and trp leader pause sites or on termination at nine different p-independent terminators. We propose that transcript cleavage and reverse translocation are controlled in part by backsliding of the nascent transcript through an RNA-binding site.

Bacterial Proteins↗
PubMed1994

The intracellular tyrosine kinase domain of the epidermal growth factor receptor undergoes a conformational change upon autophosphorylation.

The intracellular portion of the epidermal growth factor receptor consists of a tyrosine kinase domain of approximately 290 amino acids and a COOH-terminal regulatory domain of approximately 230 amino acids that contains five sites of autophosphorylation. The effect of autophosphorylation on the conformation of the intracellular domain has been analyzed using gel filtration. Both phosphorylated and dephosphorylated forms of the intracellular domain exist as monomers and as dimers and appear to have an extended conformation. The Stokes' radii of phosphorylated monomers and dimers were larger than those of the dephosphorylated forms, indicating that the dephosphorylated form is more compact. These results indicate that a significant conformational change occurs in the intracellular portion of the epidermal growth factor receptor upon tyrosine autophosphorylation.

Animals↗
PubMed1994

Analytical solutions of Pennes bio-heat transfer equation with a blood vessel.

The heat transfer within a perfused tissue in the presence of a vessel is considered. The bio-heat transfer equation is used for the perfused tissue and a lumped capacitance analysis is used for the convection in the vessel with a constant Nusselt number. Analytical solutions are obtained for two cases: (i) the arterial temperature of the perfused blood in the bio-heat transfer equation is equal to the axially varying mixed mean temperature of the blood in the vessel and, (ii) that arterial temperature is assumed to be constant. Dimensionless equilibrium length and temperature expressions are obtained and presented.

Animals↗
PubMed1994

The use and impact of a computer-based support system for people living with AIDS and HIV infection.

CHESS (the Comprehensive Health Enhancement Support System) is an interactive, computer-based system to support people facing AIDS/HIV Infection and other health-related crises or concerns. CHESS provides information, referral to service providers, support in making tough decisions and networking to experts and others facing the same concerns. CHESS is designed to improve access to health and human services for people who would otherwise face psychological, social, economic or geographic barriers to receiving services. CHESS has been evaluated in a random-assignment study with over 200 men and women living with AIDS and HIV infection. When CHESS was placed in subjects' homes for 3-6 months, use of CHESS was extremely heavy, with the average subject using CHESS 138 times for 39 hours. Compared with a control group which did not receive CHESS, subjects who used CHESS reported significantly higher quality of life in several dimensions, including social support and cognitive functioning. Users also reported significant reductions in some types of health care costs, especially inpatient services (hospitalizations). All segments of the study population used and benefited from CHESS, including women, minorities and those subjects with lower levels of education. Thus, CHESS appears to be an effective means of delivering education and support to the diverse populations which are affected by AIDS and HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Dissection of the his leader pause site by base substitution reveals a multipartite signal that includes a pause RNA hairpin.

A key feature of transcriptional attenuation in some amino acid biosynthetic operons is a transcriptional pause that occurs immediately after synthesis of the first leader transcript secondary structure. Both RNA secondary structure and downstream DNA sequence are important for pausing at these sites; however, the precise RNA structures involved and the relative contribution of other RNA and DNA bases to pausing are unknown. We studied the effects of base substitutions upstream from the his leader pause site (immediately prior to addition of G103) to determine how nucleic acid sequences and RNA structure contribute to pausing. By testing compensatory base substitutions, we found that pausing depended in part on an RNA secondary structure containing a five base-pair stem and eight nucleotide loop, which we call the his pause RNA hairpin. The his pause hairpin forms 11 nucleotides upstream from the paused transcript 3' end and thus corresponds to only the upper portion of the larger his A:B leader transcript secondary structure. Some base substitutions in the ten nucleotides between the pause hairpin and the 3' end of the transcript increased pausing, whereas others decreased pausing. However, compensatory substitutions that restored pairing of these bases in the lower portion of the A:B secondary structure did not alter these effects. Changing the 3'-terminal nucleotide of the transcript (U102) altered both the position and strength of pausing. Thus, in addition to the downstream DNA sequence, three distinct segments of nucleic acid upstream from the nucleotide-addition site in the transcription complex contribute to pausing in different ways: the pause RNA hairpin, the 3'-proximal region of transcript or DNA template, and the 3'-terminal nucleotide. We suggest that electrostatic interaction between the pause hairpin and RNA polymerase, rather than disruption of an RNA:DNA heteroduplex, delays elongation at the his leader pause site.

Bacterial Proteins↗
PubMed1993

Kinetic and DNA-binding properties of recombinant human O6-methylguanine-DNA methyltransferase.

O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that plays an important role in chemotherapy, mutagenesis, and carcinogenesis. Recombinant human MGMT was isolated from an Escherichia coli high performance expression system and purified to homogeneity. The kinetic and DNA-binding properties of the recombinant human MGMT were studied. The purified human MGMT reacted stoichiometrically with methylated DNA under second-order rate kinetics. The rate constant with normal methylated DNA was 1 x 10(9) M-1 min-1 at 37 degrees C. The binding to DNA was the rate determining step in the repair process. Approximately eight base pairs of the DNA substrate were covered by the human MGMT protein. The affinity constant for interaction of DNA to MGMT was approximately 4.7 x 10(5) M-1. The binding to methylated DNA was also examined; the binding affinity to methylated DNA was two times higher than that to unmodified DNA. The interaction with DNA induced a conformational change in the human MGMT protein as monitored by circular dichroism and fluorescence analysis. A similar conformational change was induced by both methylated and unmodified DNA.

Base Sequence↗
PubMed1993

Stimulation regimens in Assisted Reproductive Technology (ART) programme: experience in the University Hospital, Singapore.

Ovarian stimulation is critical to the success of patients in Assisted Reproductive Technology (ART) programmes. We compared two stimulation regimes retrospectively for ART in the NUH programme. These were the 2:1 and the GnRHa-FSH/hMG regimes. The former was our first-line regime while the latter was used for cycles where there was a prior endogenous LH surge, previous poor response, or an elevated LH level between days three to five of the cycle. All cycles in our ART programme in 1991 were studied, except those for special research procedures, e.g. micro-insemination sperm transfer (MIST) cycles, a total of 241 cycles. Cancellation rates were 14.4% (21 of 146 cycles) and 37.3% (19 of 51 cycles) for the 2:1 and GnRHa-FSH/hMG regimes respectively (p > 0.001). For the 2:1 regime, the majority of cancellations were due to ovulation prior to the oocyte recovery (42.9%; nine of 21 cycles). However, for the GnRHa-FSH/hMG regime, almost all the cancellations were due to poor response (84.2%; 16 of 19 cycles). Fertilisation rates were lower for the 2:1 regime (for both IVF-ER and IVF-TET, where sperm quality was poorer) compared to the GnRHa-FSH/hMG (55.0 and 66.6% respectively; p < 0.001). Pregnancy rates were higher for the 2:1 regime when IVF-ER and IVF-TET were used (16.4% and 23.3% respectively per oocyte recovery, versus 9.8% and 18.8% respectively for the GnRHa-FSH/hMG regime).

Drug Evaluation↗
PubMed1992

Irradiation-induced expression of O6-methylguanine-DNA methyltransferase in mammalian cells.

O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein which plays an important role in chemotherapy, mutagenesis, and carcinogenesis. The specific activity of MGMT in female rat liver can be induced by approximately 20-fold by treatment of the rats with gamma-irradiation. Maximum response occurred 48 h after 15 Gy irradiation. MGMT levels in male rats were induced by only 3-fold. MGMT activity was also induced by irradiation of rat hepatoma H4IIE cells with a 3-fold increase noted after treatment with 3 Gy. Northern analysis and nuclear run-on assays indicated that the induction of MGMT was regulated at the transcriptional level. The radiation-mediated increase in MGMT was blocked by H7, a protein kinase inhibitor, but not by H89, an inhibitor of protein kinase A. Hydroxyl radicals may play a role in the induction mechanism since dimethyl sulfoxide, a radical scavenger, blocked the radiation-mediated increase in MGMT. MGMT activity was also increased by treatment of the cells with H2O2, in accordance with the involvement of activated oxygen species in the induction of MGMT. Finally, the addition of cycloheximide, an inhibitor of protein synthesis, prior to but not after irradiation, abolished the increase in MGMT activity.

Animals↗
PubMed1992

Expression of human O6-methylguanine-DNA methyltransferase in a DNA excision repair-deficient Chinese hamster ovary cell line and its response to certain alkylating agents.

A plasmid has been constructed in which the expression of human O6-methylguanine-DNA methyltransferase (MGMT) complementary DNA is driven by the Rous sarcoma virus promoter sequence. We had previously shown that transfection of this plasmid into Chinese hamster ovary (CHO) cells results in the expression of MGMT and in increased cellular resistance to N-methyl-N'-nitro-N-nitrosoguanidine and 1-(2-chloroethyl)-1-nitrosourea (CNU) but not N-nitroso-N-ethylurea (ENU). In the present study, the Rous sarcoma virus promoter-MGMT was transfected into DNA excision repair-deficient CHO UV41 cells to investigate the phenotype associated with MGMT expression in the absence of DNA excision repair. Both the UV41/MGMT and CHO/MGMT cells expressed similar levels of MGMT and exhibited a similar increased resistance to N-methyl-N'-nitro-N-nitrosoguanidine. The UV41 cells were 20-fold more sensitive to CNU than the wild-type CHO cells. Expression of MGMT increased the resistance to CNU about 6-fold in both cell lines, but the difference between the two cell lines attributable to the excision repair defect still persisted. The UV41 cells were 2- to 3-fold more sensitive than the wild-type CHO cells to the monofunctional alkylating agents 1-(2-hydroxyethyl)-1-nitrosourea and ENU, but the MGMT phenotype did not alter sensitivity. This suggests that alkylation at the O6 position of guanine has no role in cytotoxicity of ethylating agents and that monofunctional DNA damage has little role in the cytotoxicity of CNU. Since MGMT can prevent the formation of G-C interstrand cross-links formed by CNU, other excision repair-sensitive DNA adducts must play a major role in the sensitivity of UV41 cells to this bifunctional alkylating agent. These results suggest that DNA intrastrand cross-links may be major contributors to the cytotoxicity of CNU.

Animals↗
PubMed1992

Boundary element method analysis for the bioheat transfer equation.

In this paper, the boundary element method (BEM) approach is applied to solve the Pennes (1948) bioheat equation. The objective is to develop the BEM formulation and demonstrate its feasibility. The basic BEM formulations for the transient and steady-state cases are first presented. To demonstrate the usefulness of the BEM approach, numerical solutions for 2-D steady-state problems are obtained and compared to analytical solutions. Further, the BEM formulation is applied to model a conjugate problem for an artery imbedded in a perfused heated tissue. Analytical solution is possible when the conduction in the x-direction is negligible. The BEM and analytical results have very good agreement.

Algorithms↗
PubMed1992

Oocyte and embryo donation.

Oocyte and embryo donation, first reported in humans in 1983 has helped patients who do not possess functional ovarian tissues or whose oocyte cannot be used for fertilisation, to conceive. Though it is the female counterpart as the donor insemination in the male, it imposes quite different bioethical issues. The article is a review of the oocyte and embryo donation programme in general, with special discussion on regimes of Cyclic Steroid Replacement Therapy, the recruitment of oocyte donors, bioethical issues, and future applications of oocyte donation in medicine.

Embryo Transfer↗